Calcium-Triggered Exocytosis and Clathrin-Mediated Endocytosis of Synaptic Vesicles

Thierry Galli^1* and Volker Haucke^2*

¹Membrane Traffic and Neuronal Plasticity Group, INSERM U536, Institut du Fer-à-moulin, 75005 Paris, France.
²Institut für Chemie-Biochemie, Freie Universität Berlin, D-14195 Berlin, Germany.

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*Corresponding author. E-mail, thierry{at}tgalli.net (T.G.) or vhaucke{at}chemie.fu-berlin.de (V.H.)

Description

Animation 1. Slow track for synaptic vesicle retrieval by clathrin-mediated endocytosis. The animation illustrates the recruitment, calcium-triggered fusion, and clathrin-mediated endocytosis of synaptic vesicles.

Vesicles are recruited from the reserve pool that corresponds to synaptic vesicles attached to the actin cytoskeleton via synapsin. Following interaction with Munc18 and Munc13, two syntaxin-binding proteins, a "loose SNARE complex" forms between a synaptic vesicle SNARE (synaptobrevin) and a plasma membrane target SNARE (SNAP-25 and syntaxin). At this point, the synaptic vesicle is shown docked to the plasma membrane. Entry of calcium triggers a conformational change in synaptotagmin 1 that produces a "tight SNARE complex", leading to lipid bilayer fusion and release of neurotransmitter (pink). The SNARE complexes, which have been inserted into the plasma membrane, are dissociated by the action of SNAPs (not shown for simplicity) and N-ethylmaleimide sensitive factor.

Clathrin-mediated endocytosis proceeds following targeting of adaptor proteins to membranes enriched in phosphatidylinositol 4,5 bisphosphate (PIP2). Dynamin then catalyzes the fission of the emanating vesicle from the membrane. Free clathrin-coated vesicles are subsequently uncoated by hsc70, auxilin, while the vesicle PIP2 is hydrolyzed by synaptojanin in conjunction with endophilin. Finally, the proton pump restores the electrochemical gradient (not shown) and the vesicles are refilled with neurotransmitter and can re-enter the cycle.

Use the buttons to proceed through the animation, to step back, or to restart.

The animation was created by Cameron Slayden under the direction of Thierry Galli and Volker Haucke.

The animation would be useful in illustrating the SNARE concept of vesicle fusion, clathrin-mediated endocytosis and calcium-triggered exocytosis events using the synaptic vesicle as a model. Thus, the animation could be useful in neurobiology, cell biology, and biochemistry courses.

This animation is an updated version of an earlier version (see related resources below). New elements include the addition of proteins that mediate changes in lipid composition that accompany endocytosis and vesicle uncoating, and the presence of additional monomeric adaptor proteins.

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Educational Details

Learning Resource Type: Animation

Context: Undergraduate upper division, graduate, professional (degree program)

Intended Users: Teacher, learner

Intended Educational Use: Teach, learn

Discipline: Biochemistry, cell biology, neurobiology

Keywords: Endocytosis, exocytosis, vesicle, synapse, SNARE

Technical Details

Format: Shockwave Flash Objects (swf file)

Size: 213 kb

Requirements: This animation will play with Macromedia Flash 5 or higher (http://www.macromedia.com/downloads/).

Related Resources

Resource Citation Review: T. Galli, V. Haucke, Cycling of synaptic vesicles: How far? How fast! Sci. STKE 2004, re19 (2004). [Gloss] [Abstract] [Full Text]

Teaching Resource: T. Galli, V. Haucke, N. R. Gough, Synaptic vesicle fusion followed by clathrin-mediated endocytosis. Sci. STKE 2003, tr3 (2003). [Abstract] [Resource Details]

Limits for Use

Cost: Free

Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for noncommercial, course-teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.

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Citation: T. Galli, V. Haucke, Calcium-triggered exocytosis and clathrin-mediated endocytosis of synaptic vesicles. Sci. STKE 2005, tr1 (2005).

© 2005 American Association for the Advancement of Science